Morphological studies have shown that chronic administration of guanethidine to newborn and adult rats specifically and permanently destroys the cell bodies of sympathetic neurons. The objectives of the proposed research program are to determine the permanent biochemical (decreases in catecholamine levels and tyrosine hydroxylase activity in several tissues) and functional (decreases in response to nerve stimulation in the whole animal isolated perfused vascular beds) consequences of guanethidine administration to newborn and adult rats and newborns of other species. These experiments will define a model of sympathectomy with distinct advantages over currently available models in its completeness of the destruction of the sympathetic innervation of the vasculature and in its unique ability to permanently destroy sympathetic neurons in adult animals. These models of sympathectomy (administration of guanethidine to newborns and adults) will be used to study the role of the sympathetic nervous system in the development and maintenance of genetic, renal, and mineralocorticoid hypertension. The sympathetic nervous systems of genetic hypertensive rats will be destroyed in newborns, young adults, or old (7-8 months) adults by treatment with guanethidine to determine at which stage of the progression of the hypertensive disease ablation of the sympathetic nervous system can permanently alter the course of the hypertension. Similar experiments will determine the effects of sympathectomy prior to the induction of renal or mineralocorticoid hypertension. In order to determine if the specific cytotoxic effects of guanethidine on sympathetic neurons which are observed in animals also occur in humans, sympathetic ganglia will be examined at autopsy from patients who had taken guanethidine for long periods. Bibliographic references: E.M. Johnson, Jr., E. Cantor, and J.R. Douglas, Jr.: Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats. J. Pharm. Expt. Ther. 193:503-513, 1975; E.M. Johnson, Jr. and F. O'Brien: Evaluation of the permanent sympathectomy produced by the administration of guanethidine to adult rats. FASEB, April, 1975.